| 1. |
- Volpe, Giovanni, 1979, et al.
(författare)
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Roadmap for optical tweezers
- 2023
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Ingår i: Journal of Physics-Photonics. - : IOP Publishing. - 2515-7647. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects, ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in the life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nano-particle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration.
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| 2. |
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| 3. |
- Adiels, Lars, 1952-, et al.
(författare)
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Test of CP violation with K0 and K‾0 at LEAR
- 1985
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Ingår i: Physics with antiprotons at LEAR in the ACOL era. - Gif sur Yvette : Editions Frontières. - 2863320351 ; , s. 467-482
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Adiels, L., et al.
(författare)
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Experimental determination of the branching ratios proton-antiproton -> 2pi0, pi0γ and γγ at rest
- 1987
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Ingår i: Zeitschrift für Physik C Particles and Fields. - 0170-9739. ; 35:1, s. 15-19
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Tidskriftsartikel (refereegranskat)abstract
- The branching ratios of Mathematical expression annihilations into the neutral final states 2π0, π0γ, and 2γ are measured by stopping antiprotons in liquid hydrogen. They are Mathematical expression, Mathematical expression, and Bγγ<1.7×10-6 (95% c.l.). © 1987 Springer-Verlag.
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| 5. |
- Adiels, Lars, et al.
(författare)
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Experimental study of the inclusive η-spectrum from proton-antiproton annihilations at rest in liquid hydrogen
- 1989
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Ingår i: Zeitschrift für Physik C Particles and Fields. - 0170-9739 .- 1431-5858. ; 42, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- The inclusive η-momentum spectrum from Mathematical expression annihilations at rest in liquid hydrogen was measured at LEAR. Branching ratios were obtained for Mathematical expression, and ηη(8.1±3.1)×10-5. An upper limit for Mathematical expression of 1.8×10-4 at 95% CL was found. The ratio of the branching ratios is BR(ηÏvariant)/BR(ηω)=0.51-0.06+0.20. For the ratio of branching ratios into two pseudoscalar mesons, we have BR(ηπ0)/BR(Ï€0Ï€0)=0.65±0.14, BR(ηη)/BR(Ï€0Ï€0), BR(ηη′)/BR(Ï€0Ï€0) at 95% CL, and BR(ηη)/BR(ηπ0). © 1989 Springer-Verlag.
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| 6. |
- Adiels, L, et al.
(författare)
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Some results of experiment PS182 at LEAR
- 1986
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Ingår i: Antiproton 86. - Singspore : World Scientific Publishing. - 9971503131 ; , s. 199-204, s. 199-204
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
- Mardinoglu, Adil, 1982, et al.
(författare)
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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
- 2018
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 27:3
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Tidskriftsartikel (refereegranskat)abstract
- A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.
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| 9. |
- Mardinoglu, Adil, 1982, et al.
(författare)
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Personal model-assisted identification of NAD(+) and glutathione metabolism as intervention target in NAFLD
- 2017
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD(+) and glutathione (GSH) in subjects with high HS. Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting. Quantification of the hepatic expression levels of the associated enzymes further pointed to altered de novo GSH synthesis. To assess the effect of GSH and NAD(+) repletion on the development of NAFLD, we added precursors for GSH and NAD(+) biosynthesis to the Western diet and demonstrated that supplementation prevents HS in mice. In a proof-of-concept human study, we found improved liver function and decreased HS after supplementation with serine (a precursor to glycine) and hereby propose a strategy for NAFLD treatment.
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| 10. |
- Richter, B., et al.
(författare)
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New results in the search for narrow states in the p system below threshold
- 1983
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 126:3-4, s. 284-288
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Tidskriftsartikel (refereegranskat)abstract
- The γ-ray spectrum after p annihilation at rest was measured in two independent high-statistics runs. Both spectra show narrow peaks, corresponding to masses of 1210, 1638, 1694 and 1771 MeV.
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| 11. |
- Taskinen, M. R., et al.
(författare)
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Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations
- 2022
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Apolipoprotein C-III (apoC-III) is a regulator of triglyceride (TG) metabolism, and due to its association with risk of cardiovascular disease, is an emergent target for pharmacological intervention. The impact of substantially lowering apoC-III on lipoprotein metabolism is not clear.METHODS. We investigated the kinetics of apolipoproteins B48 and B100 (apoB48 and apoB100) in chylomicrons, VLDL1, VLDL2, IDL, and LDL in patients heterozygous for a loss-of-function (LOF) mutation in the APOC3 gene. Studies were conducted in the postprandial state to provide a more comprehensive view of the influence of this protein on TG transport.RESULTS. Compared with non-LOF variant participants, a genetically determined decrease in apoC-III resulted in marked acceleration of lipolysis of TG-rich lipoproteins (TRLs), increased removal of VLDL remnants from the bloodstream, and substantial decrease in circulating levels of VLDL1, VLDL2, and IDL particles. Production rates for apoB48-containing chylomicrons and apoB100-containing VLDL1 and VLDL2 were not different between LOF carriers and noncarriers. Likewise, the rate of production of LDL was not affected by the lower apoC-III level, nor were the concentration and clearance rate of LDL-apoB100.CONCLUSION. These findings indicate that apoC-III lowering will have a marked effect on TRL and remnant metabolism, with possibly significant consequences for cardiovascular disease prevention. TRIAL REGISTRATION. ClinicalTrials.gov NCT04209816 and NCT01445730.
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| 12. |
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| 13. |
- Adiels, L., et al.
(författare)
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Experimental determination of the branching ratios {Mathematical expression}, and 2γ at rest
- 1987
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Ingår i: Zeitschrift für Physik C Particles and Fields. - : Springer. - 0170-9739 .- 1431-5858. ; 35:1, s. 15-19
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Tidskriftsartikel (refereegranskat)abstract
- The branching ratios of {Mathematical expression} annihilations into the neutral final states 2π 0, π 0γ, and 2γ are measured by stopping antiprotons in liquid hydrogen. They are {Mathematical expression}, {Mathematical expression}, and B γγ<1.7×10 -6 (95% c.l.).
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| 14. |
- Adiels, L., et al.
(författare)
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Experimental study of the inclusive η-spectrum from p {Mathematical expression} annihilations at rest in liquid hydrogen
- 1989
-
Ingår i: Zeitschrift für Physik C Particles and Fields. - : Springer. - 0170-9739 .- 1431-5858. ; 42:1, s. 49-58
-
Tidskriftsartikel (refereegranskat)abstract
- The inclusive η-momentum spectrum from {Mathematical expression} annihilations at rest in liquid hydrogen was measured at LEAR. Branching ratios were obtained for {Mathematical expression}, and ηη(8.1±3.1)×10 -5. An upper limit for {Mathematical expression} of 1.8×10 -4 at 95% CL was found. The ratio of the branching ratios is BR(ηρ{variant})/BR(ηω)=0.51 -0.06 +0.20. For the ratio of branching ratios into two pseudoscalar mesons, we have BR(ηπ 0)/BR(π 0π 0)=0.65±0.14, BR(ηη)/BR(π 0π 0), BR(ηη ′)/BR(π 0π 0) at 95% CL, and BR(ηη)/BR(ηπ 0). © 1989 Springer-Verlag.
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| 15. |
- Adiels, L., et al.
(författare)
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Pi0 and eta spectra from proton-antiproton annihilations at rest
- 1984
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Ingår i: Zeitschrift für Physik. C, Particles and fields. - 0170-9739. ; 21:4, s. 315-319
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Tidskriftsartikel (refereegranskat)abstract
- The low-energy part of the Ï€0 spectrum associated with Mathematical expression annihilation at rest was measured in order to search for bound baryonium-like states. The upper limit for reaching such states via the emission of monochromatic Ï€0’s was found to be 8% per annihilation in the mass region of 1650 MeV. The low-energy part of the η spectrum from Mathematical expression annihilations at rest was also observed.
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| 16. |
- Adiels, Martin, 1976, et al.
(författare)
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Acute suppression of VLDL(1) secretion rate by insulin is associated with hepatic fat content and insulin resistance
- 2007
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:11, s. 2356-2365
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver fat content. METHODS: A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group. RESULTS: The results showed a rapid drop in VLDL(1)-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin infusion whereas VLDL(2) secretion increased. CONCLUSIONS/INTERPRETATION: Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat is associated with lack of VLDL(1) suppression in response to insulin.
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| 17. |
- Adiels, Martin, 1976, et al.
(författare)
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Niacin action in the atherogenic mixed dyslipidemia of metabolic syndrome: Insights from metabolic biomarker profiling and network analysis
- 2018
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Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874. ; 12:3, s. 810-821
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Niacin as an adjunct to statin treatment to reduce cardiovascular risk is questioned. OBJECTIVE: To evaluate interrelationships between the effects of niacin on mixed dyslipidemia and a spectrum of metabolic and inflammatory biomarkers. METHODS: Obese, nondiabetic, hypertriglyceridemic males (n = 19) with low high-density lipoprotein cholesterol levels received extended-release nicotinic acid for 8 weeks. Multiple biomarkers were measured using enzyme-linked immunosorbent assay, enzymatic/absorptiometric, or multiplex biochip assays. Treatment effects were determined for each variable and a differential correlation network created on the basis of univariate correlations between baseline and response to niacin treatment for all pairs of variables. RESULTS: Extended-release niacin treatment favoured normalization of plasma lipid and apolipoprotein profile. Plasma markers of inflammation, hepatic function, cellular adhesion and proliferation, and macrophage phenotype were attenuated; however, insulin resistance increased. Differential network analysis revealed that changes in triglycerides and high-density lipoprotein cholesterol were closely linked; equally, niacin mediated reductions in total cholesterol, apolipoprotein B, low-density lipoprotein cholesterol and lipoprotein(a) clustered together, as did homeostatic model assessment of insulin resistance, insulin, and interleukin-6 levels. Two clusters of inflammatory markers were identified, involving (1) intercellular adhesion molecule 1 and high-sensitive C-reactive protein and (2) soluble tumor necrosis factor receptors; and novel clusters involving matrix metallopeptidase 9 and apolipoprotein E, and adiponectin and cystatin C, respectively, were equally revealed. At lower stringency, lipid and insulin resistance clusters were linked; a C-reactive protein-centered cluster linked reduction in apolipoprotein Cu to intercellular adhesion molecule 1, gamma-glutamyltransferase, soluble tumor necrosis factor receptors, and E-selectin. CONCLUSION: A niacin-mediated trend to normalize atherogenic mixed dyslipidemia was intimately linked to attenuation of biomarkers of inflammation, cell adhesion, hepatic dysfunction and cell proliferation, but to enhanced insulin resistance and plasma homocysteine elevation. (C) 2018 National Lipid Association. Published by Elsevier Inc.
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| 18. |
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| 19. |
- Blüm, P., et al.
(författare)
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A modular NaI(Tl) detector for 20-1000 MeV photons
- 1983
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Ingår i: Nuclear Instruments and Methods in Physics Research. - : Elsevier BV. - 0167-5087. ; 213:2-3, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- A detector consisting of 54 NaI (Tl) modules is described. The detector has been optimized for the detection of 20-1000 MeV photons. An energy resolution (fwhm) of 5.5% at 130 MeV could be attained, and the stability has been better than 1% over several months.
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| 20. |
- Adiels, Lars, et al.
(författare)
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A π0 and η spectrometer of lead glass and BGO for momenta up to 1 GeV/c
- 1986
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 244:3, s. 380-390
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Tidskriftsartikel (refereegranskat)abstract
- A spectrometer consisting of two sets of bismuth germanium oxide (BGO) crystals and a lead-glass array has been used to measure the [pi]0 and [eta] momentum spectra produced from proton-antiproton annihilations at rest. We describe the test of the BGO sets in electron beams of energies from 50 to 450 MeV. We discuss the method of construction and calibration of the lead-glass array, as well as procedures to extract the energy and position resolutions for detected photons. A momentum resolution ([sigma]) for [pi]0’s and [eta]’s of 4% and 3%, respectively has been achieved at momenta below 1 GeV/c.
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| 21. |
- Adiels, L., et al.
(författare)
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Investigations on baryonium and other rare pmacrp annihilation modes using high resolution pi0 spectrometers (PS 182)
- 1985
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Ingår i: Antiproton 1984. Proceedings of the VII European Symposium on Antiproton Interactions. - : Institution of Electrical Engineers (IEE). ; , s. 297-304
-
Konferensbidrag (refereegranskat)abstract
- In the search for heavy, narrow exotic states such as baryonium or glueballs, carried out so far, various methods of high- and low-energy production, low-energy formation, and e+e- reactions were used. In particular, a search for baryonium states below threshold (mxlsimmppmacr) has shown some evidence [Richter et al., 1983, Brando et al., 1984] for a few states. However, the results of these measurements suffer from poor statistics. Among the possible methods which can be applied in the baryonium bound state research at LEAR, the authors consider the study of the reaction ppmacrrarrX+pi0 as the most promising. They have performed an experiment to study this reaction by means of an experimental set-up especially tailored for measuring monoenergetic pi0,s, allowing for both angular distribution measurements and high-resolution spectroscopy. They report on the preliminary results from our actual measurements of the inclusive pi0 and eta spectra following the antiproton annihilation at rest.
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| 22. |
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| 23. |
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| 24. |
- Adiels, L., et al.
(författare)
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Search for narrow exotic states in annihilations on 4He
- 1984
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 138:1-3, s. 235-240
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Tidskriftsartikel (refereegranskat)abstract
- After having found evidence for narrow exotic states in p annihilation, the production of such states on a nuclear target was studied with similar techniques. The γ spectrum associated with annihilation on 4He at rest was measured. The spectrum shows two peaks, at energies of 161.9 and 203.0 MeV, corresponding to intermediate narrow states of masses which seem to be related to states found in p annihilations. The confidence is better than 4 σ.
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| 25. |
- Adiels, L., et al.
(författare)
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Search for narrow signals in the [gamma]-spectrum from [Proton-antiproton] annihilation at rest
- 1986
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 182:3-4, s. 405-408
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Tidskriftsartikel (refereegranskat)abstract
- The [gamma]-spectrum originating from pp[combining macron] annihilations at rest in liquid hydrogen was measured with two BGO spectrometers. A total of 24 ï¿œ 106[gamma]’s were accumulated. No narrow peaks indicating exotic states such as baryonium were observed. The upper limit for the branching ratio with 1040 [less-than-or-equals, slant] mx [less-than-or-equals, slant] 1770 MeV/c2 and with [lambda]x [less-than-or-equals, slant] 25 MeV/c2 is less than 10-3 with more than 99.96% confidence.
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| 26. |
- Adiels, L., et al.
(författare)
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Search for narrow signals in the γ-spectrum from pp̄ annihilation at rest
- 1986
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Ingår i: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 182:3-4, s. 405-408
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Tidskriftsartikel (refereegranskat)abstract
- The γ-spectrum originating from pp̄ annihilations at rest in liquid hydrogen was measured with two BGO spectrometers. A total of 24 × 10 6 γ's were accumulated. No narrow peaks indicating exotic states such as baryonium were observed. The upper limit for the branching ratio p p ̄ → γ + X with 1040 ≤ m x ≤ 1770 MeV/c 2 and with λ x ≤ 25 MeV/c 2 is less than 10 -3 with more than 99.96% confidence. © 1986.
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| 27. |
- Adiels, L, et al.
(författare)
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π0 and η spectroscopy at LEAR
- 1985
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Ingår i: Physics with antiprotons at LEAR in the ACOL era. - Gif sur Yvette : Editions Frontières. - 2863320351 ; , s. 359-360
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Adiels, Martin, 1976, et al.
(författare)
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A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions
- 2005
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Ingår i: J Lipid Res. - 0022-2275 .- 1539-7262. ; 46:1, s. 58-67
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Tidskriftsartikel (refereegranskat)abstract
- The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and [(2)H(5)]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population. Analysis of the correlations showed that plasma TG was determined by the VLDL(1) and VLDL(2) apoB and TG fractional catabolic rate. Furthermore, the model showed a linear correlation between VLDL(1) TG and apoB production. A novel observation was that VLDL TG entered the circulation within 21 min after its synthesis, whereas VLDL apoB entered the circulation after 33 min. These observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial apoB-containing particle in the liver.
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| 29. |
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| 30. |
- Adiels, Martin, 1976, et al.
(författare)
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Overproduction of large VLDL particles is driven by increased liver fat content in man
- 2006
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:4, s. 755-65
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production. METHODS: A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI. RESULTS: Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB. CONCLUSIONS/INTERPRETATION: We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
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| 31. |
- Adiels, Martin, 1976, et al.
(författare)
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Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia
- 2005
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Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636 .- 1079-5642. ; 25:8, s. 1697-703
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We sought to compare the synthesis and metabolism of VLDL1 and VLDL2 in patients with type 2 diabetes mellitus (DM2) and nondiabetic subjects. METHODS AND RESULTS: We used a novel multicompartmental model to simultaneously determine the kinetics of apolipoprotein (apo) B and triglyceride (TG) in VLDL1 and VLDL2 after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Our results show that the overproduction of VLDL particles in DM2 is explained by enhanced secretion of VLDL1 apoB and TG. Direct production of VLDL2 apoB and TG was not influenced by diabetes per se. The production rates of VLDL1 apoB and TG were closely related, as were the corresponding pool sizes. VLDL1 and VLDL2 compositions did not differ in subjects with DM2 and controls, and the TG to apoB ratio of newly synthesized particles was very similar in the 2 groups. Plasma glucose, insulin, and free fatty acids together explained 55% of the variation in VLDL1 TG production rate. CONCLUSIONS: Insulin resistance and DM2 are associated with excess hepatic production of VLDL1 particles similar in size and composition to those in nondiabetic subjects. We propose that hyperglycemia is the driving force that aggravates overproduction of VLDL1 in DM2.
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| 32. |
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| 33. |
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| 34. |
- Björck, Lena, 1959, et al.
(författare)
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Changes in Dietary Fat Intake and Projections for Coronary Heart Disease Mortality in Sweden: A Simulation Study
- 2016
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In Sweden, previous favourable trends in blood cholesterol levels have recently levelled off or even increased in some age groups since 2003, potentially reflecting changing fashions and attitudes towards dietary saturated fatty acids (SFA). We aimed to examine the potential effect of different SFA intake on future coronary heart disease (CHD) mortality in 2025. METHODS: We compared the effect on future CHD mortality of two different scenarios for fat intake a) daily SFA intake decreasing to 10 energy percent (E%), and b) daily SFA intake rising to 20 E%. We assumed that there would be moderate improvements in smoking (5%), salt intake (1g/day) and physical inactivity (5% decrease) to continue recent, positive trends. RESULTS: In the baseline scenario which assumed that recent mortality declines continue, approximately 5,975 CHD deaths might occur in year 2025. Anticipated improvements in smoking, dietary salt intake and physical activity, would result in some 380 (-6.4%) fewer deaths (235 in men and 145 in women). In combination with a mean SFA daily intake of 10 E%, a total of 810 (-14%) fewer deaths would occur in 2025 (535 in men and 275 in women). If the overall consumption of SFA rose to 20 E%, the expected mortality decline would be wiped out and approximately 20 (0.3%) additional deaths might occur. CONCLUSION: CHD mortality may increase as a result of unfavourable trends in diets rich in saturated fats resulting in increases in blood cholesterol levels. These could cancel out the favourable trends in salt intake, smoking and physical activity.
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| 35. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
- 2012
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 44:12, s. 1037-1041
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n=4047). Methods: We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity. Results: A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value=0.001), but not in the surgery group (log-rank P-value=0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5-23.8; P-value=0.013) of developing hepatocellular carcinoma was observed only in the control group. Conclusion: The current study is the first prospective report showing the association of the PNPLA3I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
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| 36. |
- Guigas, R., et al.
(författare)
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Strong interaction effects in antiprotonic 6Li/7Li atoms
- 1984
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 137:56, s. 323-328
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Tidskriftsartikel (refereegranskat)abstract
- The effects of strong interaction on the 3 –> 2 X-ray transition in antiprotonic 6Li/7Li atoms have been measured at the low energy -beam at CERN. For the shifts and widths of the levels the values [epsilon]2p = (-230 ï¿œ 72) eV, [Gamma]2p = (443 ï¿œ 210) eV, and [Gamma]3d = (0.130 ï¿œ 0.045) eV for 6Li, and [epsilon]2p = (-336 ï¿œ 60) eV, [Gamma]2p = (456 ï¿œ 190) eV, and [Gamma]3d = (0.210 ï¿œ 0.062) eV for 7Li were found. The data are compared with optical model predictions.
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| 37. |
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| 38. |
- Taskinen, M. R., et al.
(författare)
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Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes
- 2021
-
Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:5, s. 1191-1201
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To elucidate the impact of liraglutide on the kinetics of apolipoprotein (apo) B48- and apoB100-containing triglyceride-rich lipoproteins in subjects with type 2 diabetes (T2D) after a single fat-rich meal. Materials and Methods: Subjects with T2D were included in a study to investigate postprandial apoB48 and apoB100 metabolism before and after 16 weeks on 1.8 mg/day liraglutide (n = 14) or placebo (n = 4). Stable isotope tracer and compartmental modelling techniques were used to determine the impact of liraglutide on chylomicron and very low-density lipoprotein (VLDL) production and clearance after a single fat-rich meal. Results: Liraglutide reduced apoB48 synthesis in chylomicrons by 60% (p < .0001) and increased the triglyceride/apoB48 ratio (i.e. the size) of chylomicrons (p < .001). Direct clearance of chylomicrons, a quantitatively significant pathway pretreatment, decreased by 90% on liraglutide (p < .001). Liraglutide also reduced VLDL1-triglyceride secretion (p = .017) in parallel with reduced liver fat. Chylomicron-apoB48 production and particle size were related to insulin sensitivity (p = .015 and p < .001, respectively), but these associations were perturbed by liraglutide. Conclusions: In a physiologically relevant setting that mirrored regular feeding in subjects with T2D, liraglutide promoted potentially beneficial changes on postprandial apoB48 metabolism. Using our data in an integrated metabolic model, we describe how the action of liraglutide in T2D on chylomicron and VLDL kinetics could lead to decreased generation of remnant lipoproteins.
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| 39. |
- Taskinen, M. R., et al.
(författare)
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Role of endogenous incretins in the regulation of postprandial lipoprotein metabolism
- 2022
-
Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 187:1, s. 75-84
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL. Design and methods: A group of 22 overweight/obese men was studied to determine associations between plasma levels of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) after a fat-rich meal and the production and clearance rates of apoB48- and apoB100-containing triglyceride-rich lipoproteins. Subjects were stratified by above- and below-median incretin response (area under the curve). Results: Stratification yielded subgroups that differed about two-fold in incretin response. There were neither differences in apoB48 production rates in chylomicrons or VLDL fractions nor in apoB100 or triglyceride kinetics in VLDL between men with above- vs below-median incretin responses. The men with above-median GLP-1 and GLP-2 responses exhibited higher postprandial plasma and chylomicron triglyceride levels, but this could not be related to altered kinetic parameters. No differences were found between incretin response subgroups and particle clearance rates. Conclusion: We found no evidence for a regulatory effect of endogenous incretins on contemporaneous chylomicron or VLDL metabolism following a standardised fat-rich meal. The actions of incretins at pharmacological doses may not be reflected at physiological levels of these hormones.
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| 40. |
- Adiels, L., et al.
(författare)
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Pi0 And Eta Spectroscopy At Lear
- 1986
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Ingår i: Tignes 1985, Proceedings, Physics With Antiprotons At Lear In The Acol Era. ; , s. 359-359
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Konferensbidrag (refereegranskat)
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| 41. |
- Adiels, Martin, 1976, et al.
(författare)
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Diabetic dyslipidaemia
- 2006
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Ingår i: Curr Opin Lipidol. - 0957-9672 .- 1473-6535. ; 17:3, s. 238-46
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Diabetic dyslipidaemia is a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. The increase of large type 1 very low density lipoprotein particles in type 2 diabetes initiates a sequence of events that generates atherogenic remnants, small dense low-density lipoprotein and small dense high-density lipoprotein particles. Thus, it is of great importance to elucidate the mechanisms behind the overproduction of large very low density lipoprotein particles in diabetic dyslipidaemia. This review discusses the pathophysiology of very low density lipoprotein metabolism in type 2 diabetes and recent concepts of lipid management of diabetic dyslipidaemia. RECENT FINDINGS: Results indicate that triglyceride and apolipoprotein B production in types 1 and 2 very low density lipoprotein are significantly correlated, suggesting a coupling of the two processes governing the metabolism of these lipoprotein subpopulations. Insulin resistance, hyperglycaemia, and liver fat were associated with excess hepatic production of type 1 but not type 2 very low density lipoprotein particles. These data provide support for the independent regulation of types 1 and 2 very low density lipoprotein apolipoprotein B production. SUMMARY: Recent data suggest that the assembly of very low density lipoprotein is fundamentally altered in type 2 diabetes, explaining the overproduction of large type 1 very low density lipoprotein as well as the inability of insulin to suppress production of type 1 very low density lipoprotein in type 2 diabetes. Future discoveries hopefully will delineate the regulatory steps to allow more targeted treatment of diabetic dyslipidaemia.
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| 42. |
- Adiels, Martin, 1976, et al.
(författare)
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Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia
- 2019
-
Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:8, s. 1861-1870
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Tidskriftsartikel (refereegranskat)abstract
- - Aims: To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics. Materials and Methods: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5- 2 H 3 ]leucine using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy. Results: Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC-III secretion rate (561 ± 198 vs. 652 ± 196 mg/d, P = 0.03) and apoC-III levels (10.0 ± 3.8 vs. 11.7 ± 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes. Change in apoC-III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC-III secretion rate was higher in subjects with type 2 diabetes compared with BMI-matched non-diabetic subjects (676 ± 208 vs. 505 ± 174 mg/d, P = 0.042). Conclusions: The results reveal that the secretion rate of apoC-III is associated with elevation of triglyceride-rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC-III. © 2019 John Wiley & Sons Ltd
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| 43. |
- Berglund, Martin, 1980, et al.
(författare)
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Improved Estimation of Human Lipoprotein Kinetics with Mixed Effects Models
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
-
Tidskriftsartikel (refereegranskat)abstract
- Mathematical models may help the analysis of biological systems by providing estimates of otherwise un-measurable quantities such as concentrations and fluxes. The variability in such systems makes it difficult to translate individual characteristics to group behavior. Mixed effects models offer a tool to simultaneously assess individual and population behavior from experimental data. Lipoproteins and plasma lipids are key mediators for cardiovascular disease in metabolic disorders such as diabetes mellitus type 2. By the use of mathematical models and tracer experiments fluxes and production rates of lipoproteins may be estimated. We developed a mixed effects model to study lipoprotein kinetics in a data set of 15 healthy individuals and 15 patients with type 2 diabetes. We compare the traditional and the mixed effects approach in terms of group estimates at various sample and data set sizes. We conclude that the mixed effects approach provided better estimates using the full data set as well as with both sparse and truncated data sets. Sample size estimates showed that to compare lipoprotein secretion the mixed effects approach needed almost half the sample size as the traditional method.
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| 44. |
- Björnson, Elias, 1988, et al.
(författare)
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Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects
- 2020
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:4, s. 422-438
-
Tidskriftsartikel (refereegranskat)abstract
- Background Renewed interest in triglyceride-rich lipoproteins as causative agents in cardiovascular disease mandates further exploration of the integrated metabolism of chylomicrons and very low-density lipoproteins (VLDL). Methods Novel tracer techniques and an integrated multi-compartmental model were used to determine the kinetics of apoB48- and apoB100-containing particles in the chylomicron and VLDL density intervals in 15 subjects with a wide range of plasma triglyceride levels. Results Following a fat-rich meal, apoB48 appeared in the chylomicron, VLDL1 and VLDL2 fractions in all subjects. Chylomicrons cleared rapidly from the circulation but apoB48-containing VLDL accumulated, and over the day were 3-fold higher in those with high versus low plasma triglyceride. ApoB48-containing particles were secreted directly into both the chylomicron and VLDL fractions at rates that were similar across the plasma triglyceride range studied. During fat absorption, whilst most triglyceride entered the circulation in chylomicrons, the majority of apoB48 particles were secreted into the VLDL density range. Conclusion The intestine secretes apoB48-containing particles not only as chylomicrons but also directly into the VLDL1 and VLDL2 density ranges both in the basal state and during dietary lipid absorption. Over the day, apoB48-containing particles appear to comprise about 20-25% of circulating VLDL and, especially in those with elevated triglycerides, form part of a slowly cleared 'remnant' particle population, thereby potentially increasing CHD risk. These findings provide a metabolic understanding of the potential consequences for increased CHD risk when slowed lipolysis leads to the accumulation of remnants, especially in individuals with hypertriglyceridemia.
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| 45. |
- Björnson, Elias, 1988, et al.
(författare)
-
Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics
- 2019
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:5, s. 562-577
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundTriglyceride-rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low-density lipoproteins (VLDL). MethodsMass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL1 and VLDL2 density intervals. An integrated non-steady-state multicompartmental model was constructed to describe the metabolism of apoB48- and apoB100-containing lipoproteins following a fat-rich meal, as well as during prolonged fasting. ResultsThe kinetic model described the metabolism of apoB48 in CM, VLDL1 and VLDL2. It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL1 and VLDL2. ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50mgday(-1), and the increment during absorption was about 230mgday(-1). The fractional catabolic rates for apoB48 in VLDL1 and VLDL2 were substantially lower than for apoB48 in CM. DiscussionThis novel non-steady-state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.
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| 46. |
- Björnson, Elias, 1988, et al.
(författare)
-
Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis
- 2024
-
Ingår i: Journal of the American College of Cardiology. - 0735-1097 .- 1558-3597. ; 83:3, s. 385-395
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Lipoprotein(a) (Lp(a)) is recognized as a causal factor for coronary heart disease (CHD) but its atherogenicity relative to that of low-density lipoprotein (LDL) on a per-particle basis is indeterminate. Objectives: The authors addressed this issue in a genetic analysis based on the fact that Lp(a) and LDL both contain 1 apolipoprotein B (apoB) per particle. Methods: Genome-wide association studies using the UK Biobank population identified 2 clusters of single nucleotide polymorphisms: one comprising 107 variants linked to Lp(a) mass concentration, the other with 143 variants linked to LDL concentration. In these Lp(a) and LDL clusters, the relationship of genetically predicted variation in apoB with CHD risk was assessed. Results: The Mendelian randomization-derived OR for CHD for a 50 nmol/L higher Lp(a)-apoB was 1.28 (95% CI: 1.24-1.33) compared with 1.04 (95% CI: 1.03-1.05) for the same increment in LDL-apoB. Likewise, use of polygenic scores to rank subjects according to difference in Lp(a)-apoB vs difference in LDL-apoB revealed a greater HR for CHD per 50 nmol/L apoB for the Lp(a) cluster (1.47; 95% CI: 1.36-1.58) compared with the LDL cluster (1.04; 95% CI: 1.02-1.05). From these data, we estimate that the atherogenicity of Lp(a) is approximately 6-fold (point estimate of 6.6; 95% CI: 5.1-8.8) greater than that of LDL on a per-particle basis. Conclusions: We conclude that the atherogenicity of Lp(a) (CHD risk quotient per unit increase in particle number) is substantially greater than that of LDL. Therefore, Lp(a) represents a key target for drug-based intervention in a significant proportion of the at-risk population.
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| 47. |
- Björnson, Elias, 1988, et al.
(författare)
-
Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study
- 2023
-
Ingår i: European Heart Journal. - 0195-668X. ; 44:39, s. 4186-4195
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The strength of the relationship of triglyceride-rich lipoproteins (TRL) with risk of coronary heart disease (CHD) compared with low-density lipoprotein (LDL) is yet to be resolved. Methods and results Single-nucleotide polymorphisms (SNPs) associated with TRL/remnant cholesterol (TRL/remnant-C) and LDL cholesterol (LDL-C) were identified in the UK Biobank population. In a multivariable Mendelian randomization analysis, TRL/remnant-C was strongly and independently associated with CHD in a model adjusted for apolipoprotein B (apoB). Likewise, in a multivariable model, TRL/remnant-C and LDL-C also exhibited independent associations with CHD with odds ratios per 1 mmol/L higher cholesterol of 2.59 [95% confidence interval (CI): 1.99-3.36] and 1.37 [95% CI: 1.27-1.48], respectively. To examine the per-particle atherogenicity of TRL/remnants and LDL, SNPs were categorized into two clusters with differing effects on TRL/remnant-C and LDL-C. Cluster 1 contained SNPs in genes related to receptor-mediated lipoprotein removal that affected LDL-C more than TRL/remnant-C, whereas cluster 2 contained SNPs in genes related to lipolysis that had a much greater effect on TRL/remnant-C. The CHD odds ratio per standard deviation (Sd) higher apoB for cluster 2 (with the higher TRL/remnant to LDL ratio) was 1.76 (95% CI: 1.58-1.96), which was significantly greater than the CHD odds ratio per Sd higher apoB in cluster 1 [1.33 (95% CI: 1.26-1.40)]. A concordant result was obtained by using polygenic scores for each cluster to relate apoB to CHD risk. Conclusion Distinct SNP clusters appear to impact differentially on remnant particles and LDL. Our findings are consistent with TRL/remnants having a substantially greater atherogenicity per particle than LDL.
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| 48. |
- Borén, Jan, 1963, et al.
(författare)
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Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity Multicenter Tracer Kinetic Study
- 2015
-
Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 35:10, s. 2218-2224
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL1) triglycerides. Approach and Results A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (r=0.44, P<0.01; r=0.45, P<0.01) and fractional catabolism (r=0.49, P<0.001; r=0.55, P<0.001) of VLDL1-triglycerides and VLDL1-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL1-triglycerides (r=0.56, P<0.001) and VLDL1-apoB (r=0.53, P<0.001). Plasma apoC-III concentration was independently and inversely associated with the fractional catabolisms of VLDL1-triglycerides (r=0.48, P<0.001) and VLDL1-apoB (r=0.51, P<0.001). Conclusions Plasma triglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity.
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| 49. |
- Djekic, Demir, et al.
(författare)
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Body Mass Index in Adolescence and Long-Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke
- 2022
-
Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:21
-
Tidskriftsartikel (refereegranskat)abstract
- Background We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF. Methods and Results We conducted a nationwide, register-based, cohort study of 1 704 467 men (mean age, 18.3 +/- 0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow-up of 32 years (interquartile range, 24-41 years), 36 693 cases (mean age at diagnosis, 52.4 +/- 10.6 years) of AF were recorded. The multivariable-adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03-1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m(2) to 3.72 (95% CI, 2.44-5.66) among men with BMI of 40.0 to 50.0 kg/m(2), compared with those with BMI of 18.5 to <20.0 kg/m(2). During a median follow-up of approximate to 6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischemic stroke. The multivariable-adjusted HRs for all-cause mortality, incident heart failure, and ischemic stroke in AF-diagnosed men with baseline BMI >30 kg/m(2) compared with those with BMI <20 kg/m(2) were 2.86 (95% CI, 2.30-3.56), 3.42 (95% CI, 2.50-4.68), and 2.34 (95% CI, 1.52-3.61), respectively. Conclusions Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all-cause mortality, incident heart failure, and ischemic stroke.
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| 50. |
- Drevinge, Christina, 1983, et al.
(författare)
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Perilipin 5 is protective in the ischemic heart
- 2016
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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